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Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 181 records · Page 10Linked to original sources
PubMed1992

The effect of hydrochlorothiazide on the enhanced coughing associated with treatment with enalapril.

The effect of hydrochlorothiazide, a diuretic which is used in the treatment not only of edema but also of hypertension, on coughs associated with treatment with enalapril was studied in guinea pigs. Chronic treatment with enalapril markedly and dose dependently enhanced the number of capsaicin-induced coughs. However, chronic treatment with hydrochlorothiazide significantly reduced the number of coughs associated with enalapril treatment, also in a dose-dependent manner. These results suggest that diuretics might be used to reduce the coughing associated with treatment with inhibitors of angiotensin-converting enzyme in patients with hypertension.

Animals↗
PubMed1992

Antitussive effects of Ca2+ channel antagonists.

The effects of Ca2+ channel antagonists on the capsaicin-induced cough reflex in guinea pigs were studied. Intraperitoneal injection of nifedipine, verapamil and flunarizine in doses that ranged from 0.3 to 3.0 mg/kg decreased the number of coughs in a dose-dependent manner. These Ca2+ channel antagonists exhibited antitussive effects in the following order of potency: flunarizine = verapamil greater than nifedipine. Pretreatment with a low dose of nifedipine (0.3 mg/kg), which by itself had no significant effect on the number of coughs, markedly increased the antitussive effects of morphine, dihydrocodeine and dextromethorphan. These data suggest that Ca2+ channels play an important role in the regulation of the cough reflex.

Animals↗
PubMed1992

Streptozotocin-induced diabetes selectively alters the potency of analgesia produced by mu-opioid agonists, but not by delta- and kappa-opioid agonists.

To investigate the possible mechanisms of the alterations in morphine-induced analgesia observed in diabetic mice, we examined the influence of streptozotocin-induced (STZ-induced) diabetes on analgesia mediated by the different opioid receptors. The antinociceptive potency of morphine (10 mg/kg), administered s.c., as determined by both the tail-pinch and the tail-flick test, was significantly reduced in diabetic mice as compared to that in controls. Mice with STZ-induced diabetes had significantly decreased sensitivity to intracerebroventricularly (i.c.v.) administered mu-opioid agonists, such as morphine (10 micrograms) and [D-Ala2,N-Me Phe4,Gly-ol5]enkephalin (DAMGO, 0.5 micrograms). However, i.c.v. administration of [D-Pen2,5]enkephalin (DPDPE, 5 micrograms), a delta-opioid agonist, and U-50,488H (50 micrograms), a kappa-opioid agonist, produced pronounced antinociception in both control and diabetic mice. Furthermore, there were no significant differences in antinociceptive potency between diabetic and control mice when morphine (1 microgram), DAMGO (10 micrograms), DPDPE (0.5 micrograms) or U-50,488H (50 micrograms) was administered intrathecally. In conclusion, mice with STZ-induced diabetes are selectively hyporesponsive to supraspinal mu-opioid receptor-mediated antinociception, but they are normally responsive to activation of delta- and kappa-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Naloxone-induced analgesia in diabetic mice.

We evaluated the effects of s.c. administration of naloxone in mice with streptozotocin-induced diabetes, compared to those in age-matched naive mice. Naloxone injected s.c. produced a dose-related increase in tail-flick latency in diabetic mice but not in naive mice. Naloxone-induced analgesia in diabetic mice was significantly reduced by pretreatment with naltrindole, a selective antagonist of delta-opioid receptors. These results indicate that naloxone-induced 'paradoxical' analgesia in diabetic mice may be mediated by delta-opioid receptors.

Analgesia↗
PubMed1992

Involvement of mu-opioid receptors in the antitussive effects of pentazocine.

The effect of pentazocine on the capsaicin-induced cough reflex in rats was investigated. Intraperitoneal injection of pentazocine, in doses from 1 to 10 mg/kg, significantly decreased the number of coughs in a dose-dependent manner. The antitussive effect of pentazocine (10 mg/kg, i.p.) was significantly reduced by prior injection of naloxone (0.3 mg/kg, i.p.), but it was unaffected by Mr-2266 BS (5 mg/kg, i.p.), an antagonist of kappa-opioid receptors. The antinociceptive potency of pentazocine (30 mg/kg, i.p.), as determined by the formalin test, was significantly reduced by pretreatment with Mr-2266 BS (5 mg/kg, i.p.), whereas naloxone (0.3 mg/kg, i.p.) had no significant effect on the antinociceptive effect of pentazocine. The antitussive effects of pentazocine (3 mg/kg) and morphine (0.1 mg/kg) were significantly enhanced in rats treated chronically with naloxone (5 mg/kg/day, 5 days), whereas the antitussive effect of U-50,488 H (1 mg/kg, i.p.), a selective kappa-opioid agonist, was not enhanced in these rats. By contrast, the antinociceptive effect of morphine (0.01 mg/kg, i.p.) was significantly enhanced in rats that had been pretreated chronically with naloxone. However, the antinociceptive effects induced by pentazocine (3 mg/kg, i.p.) and U-50,488 H (1 mg/kg, i.p.) were unchanged. These results suggest that pentazocine-induced antitussive effects in rats are mediated via stimulation of mu-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Functional changes in vascular smooth muscle and endothelium of arteries during diabetes mellitus.

To investigate the influence of diabetes mellitus on the responsiveness of the vascular smooth muscle, the effects of various vasoactive agents on the reactivity of the vascular smooth muscle from diabetic animals have been undertaken, focusing on the functional changes in the endothelium, alpha-adrenoceptors, beta-adrenoceptors, voltage-dependent Ca(2+)-channels, receptor-operated Ca(2+)-channels, phosphatidylinositol turnover and potassium channels. Among the functional changes, it is a common phenomenon that decreases in acetylcholine-induced production of cyclic GMP are due to the attenuation of release of endothelium-derived relaxing factor through an impairment of endothelium; this observation was found in both rats and rabbits with diabetes mellitus. These functional changes in diabetes may be responsible for the vascular complications such as coronary heart disease, cerebrovascular disease, and an acceleration in atherosclerosis.

Animals↗
PubMed1992

Changes in responsiveness of the aorta to vasorelaxant agents in genetically diabetic rats: a study in WBN/Kob rats.

The effects of various vasorelaxant agents on aortas from control and genetically diabetic rats were examined. The concentration-response curves for the isoproterenol (ISO)-induced relaxation of both aortic strips with and without endothelium are shifted to the right in diabetic rats. The relaxation responses of diabetic aorta to forskolin and vasoactive intestinal peptide did not differ from those of controls. The relaxation responses of diabetic aorta to cromakalim and nicorandil did not differ from those of controls. These results indirectly indicate that ISO-induced relaxation responses of the aortic strips from genetically diabetic rats decreased, and that this decreased relaxation response of the strips to ISO may be due to decreased density or affinity of beta adrenoceptors on the endothelium and vascular smooth muscle.

Animals↗
PubMed1992

Preparation of multiply deuterium-labeled cortisol.

Cortisol labeled with four deuterium atoms at chemically stable sites ([9,11,12,12-(2)H4]cortisol, cortisol-d4) was prepared by hydrogen-deuterium exchange and reductive deuteration reactions. After protecting the C-17 dihydroxyacetone side chain of cortisone (cortisone-BMD), hydrogen-deuterium exchange was carried out with 6.5% NaOD in MeOD, which was followed by protection of the C-3 carbonyl as the semicarbazone. Subsequent reductive deuteration at C-11 with NaBD4 followed by removal of exchangeable deuterium under the same exchange-reaction conditions in a medium of 6.5% NaOH in MeOH and deprotection afforded the desired cortisol-d4 with high isotopic content (d3, 21.2%; d4, 78.1%; d5, 0.74%). The method was applied to the synthesis of cortisol labeled with nine deuterium atoms [( 1,1,9,11,12,12,19,19,19-(2)H9]cortisol, cortisol-d9) starting from [1,1,19,19,19-(2)H5]cortisone (cortisone-d5).

Cortisone↗
PubMed1992

A pertussis toxin-sensitive mechanism of endothelin action in porcine coronary artery smooth muscle.

1. Endothelin-1 (ET-1)-induced contraction of porcine coronary artery strips may be mediated via at least two intracellular signalling mechanisms, the activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels and the stimulation of phosphoinositide breakdown. Here we have investigated the possible involvement of pertussis toxin (PT)-sensitive guanosine-5'-triphosphate (GTP)-binding proteins (G-proteins) in ET-1-induced activation of these two signalling pathways in porcine coronary artery smooth muscle. 2. Increase in extracellular K+ concentration (10, 15 mM) shifted the dose-response relationship for the ET-1-induced contraction to the left. 3. The dihydropyridine Ca2+ channel blocker, nifedipine (10(-8) M), induced a rightward shift in the dose-response curve for ET-1. Pretreatment of the arterial strips with PT (0.1 microgram ml-1) induced a similar rightward shift of the ET-1 dose-response curve but not of the KCl response. Nifedipine (10(-8) M) did not further attenuate the ET-1-induced contraction in the PT-pretreated strips. 4. The pretreatment with PT significantly reduced 45Ca2+ uptake of the arterial strips stimulated by ET-1, but had no effect on ET-1-induced production of inositol phosphates. 5. The contractile response of the arterial strips to phorbol dibutyrate, an active phorbol ester, was not significantly affected by 10(-8) M nifedipine. 6. We confirmed that the pretreatment of the tissue with PT induced ADP-ribosylation of a 41 kDa membrane protein. 7. These findings indicate that activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels by ET-1 in this tissue is mediated via a PT-sensitive G-protein in a manner apparently independent of the ET-1-induced activation of protein kinase C. It is concluded that the action of ET-1 in porcine coronary artery is mediated via two distinct signal transduction pathways, which are coupled to PT-sensitive and PT-insensitive GTP-binding proteins, respectively.

Adenosine Diphosphate Ribose↗
PubMed1992

Age-related changes in endothelium-dependent relaxation in aorta from genetically diabetic WBN/Kob rats.

Experiments were designed to investigate the effects of aging and hyperglycemia on relaxation of the aorta for both endothelium-dependent and -independent agents in Wistar (control) and WBN/Kob (genetically diabetic) rats. The concentration of glucose in serum was elevated significantly in aged (90-92 wk) but not young (13-15 wk) WBN/Kob rats. Endothelium-dependent relaxations of both control and WBN/Kob rats to acetylcholine were reduced by aging. The relaxations induced by acetylcholine in aortic strips were significantly attenuated in both young (nondiabetic) and aged (diabetic) WBN/Kob rats, compared with those from age-matched control vessels, respectively. The concentration-response curves for sodium nitroprusside in aortic strips from both aged control and aged WBN/Kob rats were shifted to the left when compared with those from young rats, respectively. However, the maximal relaxation responses to sodium nitroprusside showed no difference among all vessels studied. The relaxations induced by sodium nitroprusside in aortic strips from both young and aged WBN/Kob rats were similar to those from age-matched control rats, respectively. The relaxations induced by atrial natriuretic peptide showed no difference among all vessels studied. In genetically diabetic rats, functional changes in endothelium occurred before elevation of the levels of glucose in the serum. Thus impaired endothelium-dependent relaxation may play an important role in the high incidence of vascular complications in diabetes mellitus.

Acetylcholine↗
PubMed1992

[Molecular pharmacology of endothelin in the cardiovascular system].

Endothelin-1 (ET-1), ET-2 and ET-3 are 21-amino acid peptides that act to stimulate contraction of many smooth muscle tissues including blood vessels, uterus, bladder, and intestine. In the case of each ET, the 21-amino acid bioactive form is produced from each precursor (referred to as big ET) via specific conversion between Trp-Val (ET-1, ET-2) or Trp-Ile (ET-3). Northern blot analysis of the mRNA for the ET isoform as well as determination of the peptide itself revealed that they are independently expressed in various tissues, indicating that each isoform may play separate physiological or pathophysiological roles. However, the vascular endothelial cells appear to produce only ET-1. Since ET-1 was first discovered, the majority of investigations so far reported have been concerned with this particular peptide. This review will focus on ET-1 with respect to the regulation of its biosynthesis in endothelial cells and its precise pharmacological actions on the cardiovascular system including the cerebral, coronary and renal circulations. Sub-classification of ET receptors was made from molecular biological, biochemical as well as pharmacological points of view. The signal transduction for mechanisms of action was also explained in detail.

Animals↗
PubMed1992

Effects of morphine on responses of nociceptive ventrobasal thalamic neurons in diabetic rats.

The influence of diabetes on the effects of morphine on the responses of ventrobasal (VB) thalamic neurons to mechanical noxious stimuli were studied in chloral hydrate-anesthetized rats. Animals were rendered diabetic by an injection of streptozotocin (60 mg/kg, i.v.). Morphine (0.3 mg/kg), administered i.v., produced a reduction in the responsiveness of VB thalamic neurons to noxious stimulation in control rats. This effect was reversed by naloxone. In contrast, the inhibitory effects of morphine on the nociceptive responses of VB thalamic neurons were significantly attenuated in diabetic rats, as compared with the controls. However, there were no significant differences in inhibitory potency between diabetic and control rats when morphine (30 nM) was administered intrathecally. It seems likely that these changes in the sensitivity of VB thalamic neurons to morphine are, to some extent, the source of the reduction in the analgesic efficacy of morphine in diabetic rats.

Animals↗
PubMed1992

Antinociceptive effect of mexiletine in diabetic mice.

We examined the effect of mexiletine on the threshold for pain perception as determined by the application of mechanical noxious stimuli (tail-pinch) in diabetic mice. Mexiletine produced a pronounced analgesic effect in diabetic mice in a dose-dependent manner. Mexiletine (10(-5)M) significantly inhibited the K(+)-evoked release of substance P from the slices of spinal cord of diabetic mice. These results suggest that the reduction of release of substance P from the nociceptive afferent terminal in the spinal cord is involved in the mechanisms of mexiletine analgesia in diabetic mice.

Animals↗
PubMed1992

Changes in muscarinic responsiveness, muscarinic receptor density and Ca2+ mobilization of the urinary bladder in streptozotocin-induced diabetic rats.

Functional changes in the urinary bladder obtained from diabetic rats were investigated by determining the responsiveness to acetylcholine (ACh). Maximal contraction of the detrusor strips in response to ACh was significantly enhanced in the diabetic rats. Ca(2+)-induced contracture of the detrusor strips, which had been incubated with 10(-3) M ACh in the presence of nicardipine in Ca(2+)-free medium, was significantly augmented in diabetic rats. Ca(2+)-contracture in Ca(2+)-free, isotonic high-K+ (60 mM) medium was not changed in diabetic state. The density of muscarinic receptors to 3H-QNB was significantly higher in the bladder from diabetic rats compared to age-matched control rats. These results suggest that tone of the autonomic nervous system in the bladder may be decreased in diabetes and, thus, compensatory increase in density of muscarinic receptors may occur. Furthermore, an increased contractile response of the detrusor strips of the urinary bladder to ACh in diabetic rats also may be due to an increased influx of extracellular Ca2+ through the receptor-operated Ca2+ channels but not the voltage-dependent Ca2+ channels.

Acetylcholine↗
PubMed1992

Modulation of kappa-mediated antitussive activity in rats by a delta-agonist.

When co-administered intracisternally, the selective delta-opioid agonist [D-Pen2,5]enkephalin (DPDPE), which had no significant effect on the cough reflex, consistently and significantly decreased the antitussive potencies of kappa-receptor agonists, U-50,488H and U-62,066E. The decrease in the antitussive effects of these kappa-receptor agonists caused by DPDPE were prevented by selective delta receptor antagonist, naltrindole. These results suggest that delta receptors may play an inhibitory role in antitussive processes that are mediated by the kappa-receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Involvement of serotonergic mechanisms in the inhibitory effect of U-50,488H on glutamate-induced lethality in mice.

The present study showed the involvement of serotonergic mechanisms in the protective effect of U-50,488H, a selective agonist of kappa-opioid receptors, against glutamate-induced lethality in mice. U-50,488H (1-10 mg/kg, i.p.) protected mice to a significant extent against glutamate-induced lethality, in a dose-related manner. This protective effect was not observed in p-chlorophenylalanine- or methysergide-treated mice. These results suggested that 5-HT in the brain may play an important role in the protective effect of U-50,488H against glutamate-induced lethality.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗